| 1. |
- Jiang, X., et al.
(författare)
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Shared heritability and functional enrichment across six solid cancers
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r(g) = 0.57, p = 4.6 x 10(-8)), breast and ovarian cancer (r(g) = 0.24, p = 7 x 10(-5)), breast and lung cancer (r(g) = 0.18, p = 1.5 x 10(-6)) and breast and colorectal cancer (r(g) = 0.15, p = 1.1 x 10(-4)). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.
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| 2. |
- Johnatty, S. E., et al.
(författare)
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No evidence that GATA3 rs570613 SNP modifies breast cancer risk
- 2009
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Ingår i: Breast Cancer Research and Treatment. - : Springer. - 0167-6806 .- 1573-7217. ; 117:2, s. 371-379
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Tidskriftsartikel (refereegranskat)abstract
- GATA-binding protein 3 (GATA3) is a transcription factor that is crucial to mammary gland morphogenesis and differentiation of progenitor cells, and has been suggested to have a tumor suppressor function. The rs570613 single nucleotide polymorphism (SNP) in intron 4 of GATA3 was previously found to be associated with a reduction in breast cancer risk in the Cancer Genetic Markers of Susceptibility project and in pooled analysis of two case-control studies from Norway and Poland (P trend = 0.004), with some evidence for a stronger association with estrogen receptor (ER) negative tumours [Garcia-Closas M et al. (2007) Cancer Epidemiol Biomarkers Prev 16:2269-2275]. We genotyped GATA3 rs570613 in 6,388 cases and 4,995 controls from the Breast Cancer Association Consortium (BCAC) and 5,617 BRCA1 and BRCA2 carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). We found no association between this SNP and breast cancer risk in BCAC cases overall (ORper-allele = 1.00, 95% CI 0.94-1.05), in ER negative BCAC cases (ORper-allele = 1.02, 95% CI 0.91-1.13), in BRCA1 mutation carriers RRper-allele = 0.99, 95% CI 0.90-1.09) or BRCA2 mutation carriers (RRper-allele = 0.93, 95% CI 0.80-1.07). We conclude that there is no evidence that either GATA3 rs570613, or any variant in strong linkage disequilibrium with it, is associated with breast cancer risk in women.
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| 3. |
- Luoma, M. L., et al.
(författare)
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Physical performance, toxicity, and quality of life as assessed by the physician and the patient
- 2002
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Ingår i: Acta Oncol. - 0284-186X .- 1651-226X. ; 41:1, s. 44-9
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to study the relationship between physician-assessed quality of life parameters, i.e., toxicity and physical performance, and patients' self-reports of their quality of life (QoL). QoL was assessed at baseline and before each treatment, using the EORTC QLQ-C30. The WHO performance score (PS) and toxicity were assessed in physician interviews. The correlations between the WHO PS and the QLQ-C30 functioning scale scores varied from weak to moderate, depending on the scale. Strongest associations were found in physical-, social-, and role functioning, and in the global QoL. The QLQ-C30 nausea/vomiting and diarrhea scales correlated moderately to corresponding WHO scores. A multiple linear regression analysis was used to analyze the contribution of WHO PS and toxicity variables to the global QoL. The best model explained only 16% of the variance of the global QoL score. The present findings highlight the importance of independent QoL assessments focused on those aspects of QoL not captured in clinical interviews with the physician.
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| 4. |
- D'Urban Jackson, J., et al.
(författare)
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Polygamy slows down diversification in shorebirds
- 2017
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Ingår i: ASAB Winter Meeting 2017 (Abstract), December 7-8, Londont, UK..
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Here we introduce a novel hypothesis concerning the role of sexual selection in speciation. As an alternative to sexual selection leading to reproductive isolation, the “dispersal to mate” hypothesis predicts that sexual selection pressure may act to slow speciation since polygamous individuals can access additional mates by increased breeding dispersal. High breeding dispersal should hence increase gene flow and reduce diversification in polygamous species (i.e. species under elevated sexual selection pressure). Here we test this hypothesis to assess how polygamy affects population divergence in shorebirds using genetic differentiation and subspecies richness as proxies for diversification. Across 79 populations of ten plover species (genus: Charadrius), in addition to subspecies data from 136 shorebird species, our results suggest that dispersal associated with polygamy may facilitate gene flow and limit population divergence. Therefore, intense sexual selection, as occurring in polygamous species, may act rather as a brake than an engine of speciation in shorebirds. We encourage future research to further investigate this hypothesis using theoretical, direct tracking and genetic approaches which will inevitably improve our understanding of the relationships between sexual selection, dispersal and diversification.
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| 5. |
- D'Urban Jackson, J., et al.
(författare)
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Polygamy slows down population divergence in shorebirds
- 2017
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Ingår i: Evolution. - : Wiley. - 0014-3820. ; 71:5, s. 1313-1326
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Tidskriftsartikel (refereegranskat)abstract
- Sexual selection may act as a promotor of speciation since divergent mate choice and competition for mates can rapidly lead to reproductive isolation. Alternatively, sexual selection may also retard speciation since polygamous individuals can access additional mates by increased breeding dispersal. High breeding dispersal should hence increase gene flow and reduce diversification in polygamous species. Here, we test how polygamy predicts diversification in shorebirds using genetic differentiation and subspecies richness as proxies for population divergence. Examining microsatellite data from 79 populations in 10 plover species (Genus: Charadrius) we found that polygamous species display significantly less genetic structure and weaker isolation-by-distance effects than monogamous species. Consistent with this result, a comparative analysis including 136 shorebird species showed significantly fewer subspecies for polygamous than for monogamous species. By contrast, migratory behavior neither predicted genetic differentiation nor subspecies richness. Taken together, our results suggest that dispersal associated with polygamy may facilitate gene flow and limit population divergence. Therefore, intense sexual selection, as occurs in polygamous species, may act as a brake rather than an engine of speciation in shorebirds. We discuss alternative explanations for these results and call for further studies to understand the relationships between sexual selection, dispersal, and diversification.
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| 6. |
- Elsaid, H. O. A., et al.
(författare)
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Reduced α-galactosidase A activity in zebrafish (Danio rerio) mirrors distinct features of Fabry nephropathy phenotype
- 2022
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Ingår i: Molecular Genetics and Metabolism Reports. - : Elsevier BV. - 2214-4269. ; 31
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Tidskriftsartikel (refereegranskat)abstract
- Fabry disease (FD) is a rare genetic lysosomal storage disorder, resulting from partial or complete lack of alpha-galactosidase A (α-GAL) enzyme, leading to systemic accumulation of substrate glycosphingolipids with a broad range of tissue damage. Current in vivo models are laborious, expensive, and fail to adequately mirror the complex FD physiopathology. To address these issues, we developed an innovative FD model in zebrafish. Zebrafish GLA gene encoding α-GAL enzyme presents a high (>70%) homology with its human counterpart, and the corresponding protein has a similar tissue distribution, as evaluated by immunohistochemistry. Moreover, a similar enzymatic activity in different life stages could be demonstrated. By using CRISPR/Cas9 technology, we generated a mutant zebrafish with decreased GLA gene expression, and decreased expression of the specific gene product in the kidney. Mutant animals showed higher plasma creatinine levels and proteinuria. Transmission electron microscopy (TEM) studies documented an increased podocyte foot process width (FPW) in mutant, as compared to wild type zebrafish. This zebrafish model reliably mirrors distinct features of human FD and could be advantageously used for the identification of novel biomarkers and for an effective screening of innovative therapeutic approaches. © 2022 The Authors
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| 7. |
- Liljensten, E, et al.
(författare)
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Studies of the healing of bone grafts, and the incorporation of titanium implants in grafted bone: an experimental animal model.
- 1998
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Ingår i: Journal of materials science. Materials in medicine. - : Springer Science and Business Media LLC. - 0957-4530 .- 1573-4838. ; 9:9, s. 535-41
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Tidskriftsartikel (refereegranskat)abstract
- An insufficient quality and amount of bone often necessitate the clinical use of implants together with bone transplants. The present study describes an experimental animal model for the study of implants in bone grafts. Circular defects were made bilaterally in the tibia of 36 rabbits. The defects received either autologous cortical bone (control), demineralized bone matrix (DBM), plasma-augmented DBM or were left empty (without bone graft). In all defects a titanium implant was centrally placed and anchored in the opposite cortex. Evaluation with light microscopic morphometry showed that the insertion of a threaded titanium implant centrally in a cortical defect was followed by a spontaneous healing of the defect after 6 mon. After 6 wk, all implants in cortical grafts were well integrated with a significantly higher bone-to-implant contact than in the DBM and plasma-augmented groups. After 6 mon, all experimental groups had a mean bone area within the threads ranging between 69% and 80% and a mean bone-to-implant contact between 31% and 42%. The results from the present study indicate that the model allows comparative studies on the early formation, resorption and remodelling of bone around implants after modification of implant, graft and host properties.
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| 8. |
- Pauliny, Angela, 1972, et al.
(författare)
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Effects of male telomeres on probability of paternity in sand lizards
- 2018
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Ingår i: Biology Letters. - : The Royal Society. - 1744-9561 .- 1744-957X. ; 14:8
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Tidskriftsartikel (refereegranskat)abstract
- Standardized swim-up trials are used in in vitro fertilization clinics to select particularly motile spermatozoa in order to increase the probability of a successful fertilization. Such trials demonstrate that sperm with longer telomeres have higher motility and lower levels of DNA damage. Regardless of whether sperm motility, and successful swim-up to fertilization sites, is a direct or correlational effect of telomere length or DNA damage, covariation between telomere length and sperm performance predicts a relationship between telomere length and probability of paternity in sperm competition, a prediction that for ethical reasons cannot be tested on humans. Here, we test this prediction in sand lizards (Lacerta agilis) using experimental data from twice-mated females in a laboratory population, and telomere length in blood from the participating lizards. Female identity influenced paternity (while the mechanism was not identified), while relatively longer male telomeres predicted higher probability of paternity. We discuss potential mechanisms underpinning this result.
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| 9. |
- Rask, Gunilla, et al.
(författare)
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Correlation of tumour subtype with long-term outcome in small breast carcinomas: a Swedish population-based retrospective cohort study
- 2022
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 195:3, s. 367-377
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Tidskriftsartikel (refereegranskat)abstract
- Purpose To investigate if molecular subtype is associated with outcome in stage 1 breast cancer (BC). Methods Tissue samples from 445 women with node-negative BC <= 15 mm, treated in 1986-2004, were classified into surrogate molecular subtypes [Luminal A-like, Luminal B-like (HER2-), HER2-positive, and triple negative breast cancer (TNBC)]. Information on treatment, recurrences, and survival were gathered from medical records. Results Tumour subtype was not associated with overall survival (OS). Luminal B-like (HER2-) and TNBC were associated with higher incidence of distant metastasis at 20 years (Hazard ratio (HR) 2.26; 95% CI 1.08-4.75 and HR 3.24; 95% CI 1.17-9.00, respectively). Luminal B-like (HER2-) and TNBC patients also had worse breast cancer-specific survival (BCSS), although not statistically significant (HR 1.53; 95% CI 0.70-3.33 and HR 1.89; 95% CI 0.60-5.93, respectively). HER2-positive BC was not associated with poor outcome despite no patient receiving HER2-targeted therapy, with most of these tumours being ER+. Conclusions Stage 1 TNBC or Luminal B-like (HER2-) tumours behave more aggressively. Women with HER2+/ER+ tumours do not have an increased risk of distant metastasis or death, absent targeted treatment.
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| 10. |
- Rosenberg, Rutger, 1943, et al.
(författare)
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Marine quality assessment by use of benthic species-abundance distributions: a proposed new protocol within the European Union Water Framework Directive
- 2004
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Ingår i: Marine Pollution Bulletin. - : Elsevier BV. - 0025-326X. ; 49:9-10, s. 728-739
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study is to develop a new method for classification of marine benthic quality according to the European Union Water Framework Directive. Tolerance values to environmental disturbance were determined in an objective analysis for benthic species along the Swedish west coast by using 4676 samples from 257 stations. Based on a combination of the species tolerance values, abundance and diversity, a benthic quality index (BQI) was calculated for the assessment of environmental status at a particular station. The qualification of BQl was evaluated in relation to known spatial and temporal gradients of disturbance. (C) 2004 Elsevier Ltd. All rights reserved.
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